Ferulic acid decarboxylase (Fdc1) controls oxidative maturation of the prFMN cofactor

Arune Balaikaite, Malama Chisanga, Karl Fisher, Derren Heyes, Reynard Spiess, David Leys

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Prenylated FMN (prFMN) is a recently discovered modified flavin cofactor containing an additional non-aromatic ring, connected to the N5 and C6 atoms. This cofactor underpins reversible decarboxylation catalyzed by members of the widespread UbiD-enzyme family, and is produced by the flavin prenyltransferase UbiX. Oxidative maturation of the UbiX product prFMNH2 to the corresponding oxidized prFMNiminium is required for Fdc1 (a UbiD-type enzyme) activity. However, it is unclear what role the Fdc1-enzyme plays in this process. Here we demonstrate that in the absence of Fdc1, prFMNH2 oxidation by O2 proceeds via a transient semiquinone prFMNradical species and culminates in a remarkably stable prFMN-hydroperoxide species. Neither forms of prFMN are able to support Fdc1 activity. Instead, enzyme activation using O2-mediated oxidation requires prFMNH2 binding prior to oxygen exposure, confirming that UbiD-enzymes play a role in O2 mediated oxidative maturation. In marked contrast, alternative oxidants such as potassium ferricyanide support prFMNiminium formation both in solution and in Fdc1.
Original languageEnglish
JournalACS chemical biology
Publication statusAccepted/In press - 25 Aug 2020

Research Beacons, Institutes and Platforms

  • Manchester Institute of Biotechnology


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